P1570: SARS-COV-2 HUMORAL AND CELLULAR VACCINATION RESPONSE IN PATIENTS WITH LYMPHOID HAEMATOLOGICAL MALIGNANCIES
Authors: L. S. Boerenkamp, C. R. Pothast, R. C. Dijkland, I. H. van Loo, L. Wieten, C. J. Halkes, M. H. Heemskerk, C. H. Van Elssen
Journal: HemaSphere (2022)

Background: Patients diagnosed with hematologic malignancy (HM) are at a high risk of severe or fatal coronavirus disease 19 (COVID-19). COVID-19 is the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A large-scale vaccination program was launched globally in the battle against this virus. However, the safety and efficacy of the vaccines was only tested in healthy individuals. HM patients often suffer from malignantly transformed immune cells and/or are treated with immune depleting/suppressive treatment leading to altered immune responses to infections and vaccination. We hypothesize that a part of HM patients will have an altered, attenuated, or absent immune response to SARS-CoV-2 vaccination. Therefore, data on response and protection rates is needed to provide correct information to patients. Aims: The aim of this study is to assess the efficacy of SARS-CoV-2 vaccination, in terms of SARS-COV-2 spike antibody and T cell responses in patients diagnosed with and/or under treatment for chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). Methods: This is a multicenter prospective phase IV intervention study. Vaccine responses were evaluated pre-SARS-CoV-2 vaccination and 2 weeks, 3- and 6-months post SARS-CoV-2 vaccination. Humoral responses were evaluated by testing SARS-CoV-2 spike receptor binding domain (RBD) specific Ig. T cell responses were evaluated by CD4 and CD8 T cell stimulation with SARS-CoV-2 spike peptide followed by antibody staining for T cell activation and cytokine production analyzed by flow cytometry. Additionally CD8 T cell responses were analyzed by SARS-CoV-2 specific HLA-tetramer binding assays. Results: In total 160 patients were included, 31 were diagnosed with CLL, 39 with aggressive NHL, 57 with indolent NHL, 30 with MM and 3 with other HM. All patients initially received two doses of mRNA-1273 or BNT162b2 and part received a booster during the study. Seroconversion rates two weeks after initial vaccination were 55% in CLL, 70% in aggressive NHL, 72% in indolent NHL and 100% in MM. The rates were stable at 3 months post vaccination and increased at 6 months post vaccination for CLL and NHL patients when boostered (Table 1). Two weeks post vaccination anti-SARS-CoV-2 S-RBD titers were above the 75th percentile of the measuring area in 37% of CLL, 62% of aggressive NHL, 60% of indolent NHL and 93% of MM patients (Table 1). Seroconversion rates for NHL patients that have received anti-CD20 therapy in the last 6 months before vaccination, 6-12 months before vaccination or more than 12 months before vaccination were respectively 16%, 60% and 95% at two weeks after initial vaccination. Spike specific CD4+ T cell responses, defined by activation markers (CD137 and CD154), were confirmed in 91% of the seronegative patients at two weeks after initial vaccination. CD8 spike specific tetramer binding was also observed in seronegative patients. Image:Summary/Conclusion: Seroconversion rates are lower in patients diagnosed with CLL or NHL, but normal for MM patients. NHL patient on current or recent rituximab treatment had very low seroconversion rates, however this almost normalized when treatment was finished more than 12 months before vaccination. Antibody titers of seropositive patients with NHL or MM are mostly above the 75th percentile of the measuring area, whereas this is lower for patients with CLL. Spike specific CD4+ T cell activation and presence of SARS-CoV-2 spike specific CD8 T cells was observed despite seronegativity. Additional T cell responses are currently being analyzed and will be presented.